I. Field of the Invention
The present invention relates generally to the fields of cancer biology and medicine. More particularly, it concerns methods for the diagnosis, prevention, and treatment of carcinomas and risk factors thereof.
II. Description of Related Art
Cancer cells have the ability to co-opt multiple pathways to fulfill their increased requirement for specific metabolites (Vander Heiden, 2011). In particular, polyamine metabolism is a highly coordinated process that is associated with fundamental cellular activities, including proliferation and development (Gerner and Meyskens, 2004; Zhang et al., 2012). Polyamines are essential for both normal development and neoplastic growth in mammals, and elevated tissue levels of polyamines are frequently associated with cancers, including those of the colorectum, as a result of deregulated oncogenes and tumor suppressors (Gerner and Meyskens, 2004). Treatment of patients with agents that suppress colorectal polyamine contents dramatically reduces metachronous colorectal adenomas, which are precursors of colorectal cancers (CRC) (Meyskens et al., 2008). Furthermore, previous clinical cancer prevention trials demonstrated that polyamine metabolism is a tractable target to prevent risk of several epithelial cancers, including those of the colon, prostate and skin (Meyskens et al., 2008; Bailey et al., 2010; Simoneau et al., 2008). For example, the demonstrated marked efficacy of polyamine-inhibitory combination of long-term daily oral D,L-α-difluoromethylornithine (DFMO, eflornithine) and sulindac among colorectal adenoma (CRA) patients was recently demonstrated (Meyskens et al., 2008), however, treatment was associated with modest, subclinical ototoxicity (McLaren et al., 2008), and a greater number of cardiovascular events among patients with high baseline cardiovascular risk (Zell et al., 2009). Identifying genetic features that identify the suitability of a patient for a given preventative or curative treatment regime would be a major benefit.